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Studies in Aim 1 will determine if LLO is an immuno-dominant antigen for MHC Class Ib restricted antilisterial CTLs. Studies in Aim 2 will determine if MHC Class Ib restricted anti-listerial cells are protective in vivo. Studies in Aim 3 will identify the LLO-derived MHC Class Ib-restricted CTL epitope. Results from these studies will provide an understanding of the role of MHC Class Ib restricted effector cell in the protective immune response to an intracellular pathogen.
The protective immune response to L. monocytogenes is used to investigate cell-mediated immunity to intracellular bacteria. A necessary virulence determinant is secretion of listeriolysin O (LLO). Listeria-specific CD8+ T cells are cytotoxic in vitro, these effectors lyse L. monocytogenes infected targets. In BALB/c mice (H2d), CD8+ CTLs have been isolated which are Kd restricted, and a nanomer peptide corresponding to aa91-99 of LLO shown to be presented by the MHC Class Ia molecule. LLO-specific CD8+ T-cells have also been described which lyse L. monocytogenes infected targets in an MHC Class IB restricted manner; the antigen presenting molecule is encoded within the T-region of a less polymorphic family of MHC Class I molecules.